When focusing solely CMAs of excipients, the same principles of API apply. These attributes influence the performance and manufacturability of the final drug product and are critical for achieving consistency in pharmaceutical formulations.
Critical Material Attributes of Excipients
Physical Properties
Particle Size Distribution (PSD):
- Affects blend uniformity, flowability, compressibility, and dissolution.
- Example: Fine-grade lactose can improve compaction but may reduce flow properties.
Bulk Density and Tap Density:
- Influences blend homogeneity, dosing accuracy, and tablet weight uniformity.
Specific Surface Area:
- Affects interaction with other excipients, wettability, and dissolution.
Chemical Properties
Purity and Impurities:
- Impurities in excipients (e.g., residual solvents, heavy metals) can degrade the drug product.
pH and Buffering Capacity:
- Important for excipients like buffers or fillers, influencing stability and dissolution.
Moisture Content:
- Hygroscopicity can affect stability, hardness, and disintegration.
- Example: Excess moisture in microcrystalline cellulose can weaken tablet hardness.
Mechanical Properties
Compressibility:
- Critical for tablet manufacturing, ensuring tablets are robust but not too hard to disintegrate.
Flowability:
- Essential for uniform feeding of the material during granulation or direct compression.
Functionality-Specific Attributes
Disintegration:
- Superdisintegrants (e.g., croscarmellose sodium, sodium starch glycolate) must swell rapidly and evenly to ensure timely tablet disintegration.
Lubrication:
- Lubricants like magnesium stearate must reduce friction without affecting tablet hardness or dissolution.
Binding Properties:
- Binders like povidone or pregelatinized starch should form strong granules while maintaining tablet.
Examples of Excipient-Specific CMAs
Lactose (Filler/Diluent):
- Particle size affects compressibility and tablet hardness.
- Spray-dried lactose offers better flowability compared to anhydrous or crystalline forms.
Microcrystalline Cellulose (Binder/Filler):
- Moisture content impacts compressibility and stability.
- Bulk density affects uniform blending in the formulation.
Croscarmellose Sodium (Disintegrant):
- Degree of crosslinking determines swelling capacity and disintegration time.
- Particle size influences distribution within the tablet.
Magnesium Stearate (Lubricant):
- Specific surface area affects lubrication efficiency and dissolution retardation.
- Over-lubrication due to excessive use or fine particles can reduce tablet hardness and disintegration.
HPMC (Hydroxypropyl Methylcellulose) (Polymer):
- Viscosity grade impacts drug release in sustained-release formulations.
By identifying and controlling CMAs of excipients, manufacturers can ensure robust formulations and consistent quality while minimizing variability in the manufacturing process.
Read also:
- Excipients in Pharmaceutical Applications
- WHO GMP Guideline for Excipients Used in Pharmaceutical Products
Resource Person: Moinuddin syed. Ph.D, PMP®